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      Hop Extract: An Efficacious Antimicrobial and Anti-biofilm Agent Against Multidrug-Resistant Staphylococci Strains and Cutibacterium acnes

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          Abstract

          Bacteria belonging to Staphylococcus genus, in particular methicillin-resistant Staphylococcus aureus and multidrug-resistant Staphylococcus epidermidis, together with Cutibacterium acnes are the main strains involved in skin disease. The increase in multidrug-resistant bacteria has revived attention on natural compounds as alternative agents for the treatment management. Among these, hop extract, a hydroalcoholic solution obtained from experimental crops of Humulus lupulus L. variety cascade (hop), displays diverse biological properties including an antimicrobial one. The aim of this study was to evaluate the antimicrobial activity and the capacity to inhibit the biofilm formation of a characterized hop extract against S. aureus and S. epidermidis multidrug-resistant strains and against a C. acnes strain. The hop extract was characterized by (i) phytochemical analysis through a reversed-phase high-performance liquid chromatography (HPLC)–fluorimetric method, (ii) biocompatibility test with Artemia salina L., (iii) cytotoxicity against two cell lines, (iv) docking analysis, and (v) antimicrobial and antibiofilm activities by detection of zones inhibition, minimal inhibitory concentrations (MICs), biomass quantification, and cell viability. The hop extract was biocompatible and non-cytotoxic at all tested concentrations. HPLC analysis revealed significant levels of gallic acid, resveratrol, and rutin. This last compound was the most representative displaying a high affinity against PBP2a and KAS III (Ki values in the submicromolar range). The characterized hop extract showed a good antimicrobial action with MICs ranging from 1 to 16 μg/mL and was able to inhibit the biofilm formation of all tested strains, except for two S. aureus strains. The biofilm formed in presence of the hop extract was significantly reduced in most cases, even when present at a concentration of 1/4 MIC. The live/dead images showed a remarkable inhibition in the biofilm formation by hop extract with a weak killing action. Overall, the tested hop extract is a good candidate to further explore for its use in the prevention of infection particularly, by multidrug-resistant Gram-positive pathogens.

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          Most cited references36

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          Coagulase-negative staphylococci.

          The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides.
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            Methicillin-resistant Staphylococcus aureus

            Since the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has emerged, disseminated globally and become a leading cause of bacterial infections in both health-care and community settings. However, there is marked geographical variation in MRSA burden owing to several factors, including differences in local infection control practices and pathogen-specific characteristics of the circulating clones. Different MRSA clones have resulted from the independent acquisition of staphylococcal cassette chromosome mec (SCCmec), which contains genes encoding proteins that render the bacterium resistant to most β-lactam antibiotics (such as methicillin), by several S. aureus clones. The success of MRSA is a consequence of the extensive arsenal of virulence factors produced by S. aureus combined with β-lactam resistance and, for most clones, resistance to other antibiotic classes. Clinical manifestations of MRSA range from asymptomatic colonization of the nasal mucosa to mild skin and soft tissue infections to fulminant invasive disease with high mortality. Although treatment options for MRSA are limited, several new antimicrobials are under development. An understanding of colonization dynamics, routes of transmission, risk factors for progression to infection and conditions that promote the emergence of resistance will enable optimization of strategies to effectively control MRSA. Vaccine candidates are also under development and could become an effective prevention measure.
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              Antimicrobial activity of essential oils and other plant extracts.

              The antimicrobial activity of plant oils and extracts has been recognized for many years. However, few investigations have compared large numbers of oils and extracts using methods that are directly comparable. In the present study, 52 plant oils and extracts were investigated for activity against Acinetobacter baumanii, Aeromonas veronii biogroup sobria, Candida albicans, Enterococcus faecalis, Escherichia col, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica subsp. enterica serotype typhimurium, Serratia marcescens and Staphylococcus aureus, using an agar dilution method. Lemongrass, oregano and bay inhibited all organisms at concentrations of < or = 2.0% (v/v). Six oils did not inhibit any organisms at the highest concentration, which was 2.0% (v/v) oil for apricot kernel, evening primrose, macadamia, pumpkin, sage and sweet almond. Variable activity was recorded for the remaining oils. Twenty of the plant oils and extracts were investigated, using a broth microdilution method, for activity against C. albicans, Staph. aureus and E. coli. The lowest minimum inhibitory concentrations were 0.03% (v/v) thyme oil against C. albicans and E. coli and 0.008% (v/v) vetiver oil against Staph. aureus. These results support the notion that plant essential oils and extracts may have a role as pharmaceuticals and preservatives.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                13 August 2020
                2020
                : 11
                : 1852
                Affiliations
                [1] 1Dipartimento di Farmacia, Università degli Studi “Gabriele d’Annunzio” Chieti-Pescara , Chieti, Italy
                [2] 2LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , Porto, Portugal
                Author notes

                Edited by: Fabian Cieplik, University Hospital Regensburg, Germany

                Reviewed by: Keisuke Nakase, Tokyo University of Pharmacy and Life Sciences, Japan; Fohad Mabood Husain, King Saud University, Saudi Arabia; Thomas Stephens Wilkinson, Swansea University, United Kingdom

                *Correspondence: Luigina Cellini, l.cellini@ 123456unich.it

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.01852
                7438819
                32117092
                22e8ad20-1f49-42d8-90fc-d302895b623e
                Copyright © 2020 Di Lodovico, Menghini, Ferrante, Recchia, Castro-Amorim, Gameiro, Cellini and Bessa.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 March 2020
                : 15 July 2020
                Page count
                Figures: 5, Tables: 5, Equations: 0, References: 43, Pages: 12, Words: 0
                Funding
                Funded by: Ministero dell’Istruzione, dell’Università e della Ricerca 10.13039/501100003407
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                hop extract,staphylococcus spp. and cutibacterium acnes,antibacterial activity,antibiofilm activity,antimicrobial resistance,biocompatibility

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